Micronized placental tissue compositions and methods of making and using the same

Abstract

Described herein are compositions composed of micronized placental components, extracts of micronized placental components, and pharmaceutical compositions thereof. The compositions have numerous medical applications. Methods for making and using the micronized compositions and the extracts thereof are also described herein.

What is claimed: 
     
         1 . A pharmaceutical composition comprising micronized placental tissue selected from the group consisting of amnion, chorion, intermediate tissue layer, or any combination thereof 
     
     
         2 . The composition of  claim 1 , wherein the composition comprises micronized amnion, chorion, intermediate tissue layer, or any combination thereof as individual components. 
     
     
         3 . The composition of  claim 1 , wherein the composition comprises a micronized tissue graft comprising amnion, chorion, intermediate tissue layer, or any combination thereof 
     
     
         4 . The composition of  claim 1 , wherein the composition comprises micronized amnion and intermediate tissue layer as individual components, wherein the intermediate tissue layer has been removed from the amnion. 
     
     
         5 . The composition of  claim 4 , wherein the micronized amnion has a particle size less than 200 μm. 
     
     
         6 . The composition of  claim 4 , wherein the weight ratio of amnion to intermediate tissue layer is from 10:1 to 1:10. 
     
     
         7 . The composition of  claim 4 , wherein the weight ratio of amnion to intermediate tissue layer is from 2:1 to 1:1 and the micronized amnion and intermediate tissue layer has a particle size from 25 μm to 200 μm. 
     
     
         8 . The composition of  claim 1 , wherein the composition comprises a micronized tissue graft comprising at least two layers of chorion, at least two layers of amnion membrane, or at least one layer of chorion and amnion membrane. 
     
     
         9 . The composition of  claim 1 , wherein the composition comprises a micronized amnionlchorion tissue graft. 
     
     
         10 . The composition of  claim 9 , wherein the micronized particles have a particle size less than 400 μm. 
     
     
         11 . The composition of  claim 9 , wherein the micronized particles have a particle size from 150 μm to 350 μm. 
     
     
         12 . The composition of  claim 9 , wherein the weight ratio of chorion to amnion is from 10:1 to 1:10. 
     
     
         13 . The composition of  claim 9 , wherein the weight ratio of chorion to amnion is from 4:1 to 1:1 and the micronized particles have a particle size from 25 μm to 200 μm. 
     
     
         14 . The composition of  claim 1 , wherein the composition further comprises a filler. 
     
     
         15 . The composition of  claim 14 , wherein the filler comprises allograft pericardium, allograft acellular dermis, Wharton's jelly, purified xenograft Type-1 collagen, biocellulose polymers or copolymers, biocompatible synthetic polymer or copolymer films, purified small intestinal submucosa, bladder acellular matrix, cadaveric fascia, or any combination thereof 
     
     
         16 . The composition of  claim 14 , wherein the filler comprises Wharton's jelly. 
     
     
         17 . The composition of  claim 1 , wherein the amnion, chorion, intermediate tissue layer, or any combination thereof are cross-linked. 
     
     
         18 . The composition of  claim 1 , further comprising a bioactive agent. 
     
     
         19 . The composition of  claim 18 , wherein the bioactive agent comprises a hemostatic agent, a fibrin glue, an allograft, or an autogenous material. 
     
     
         20 . The composition of  claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         21 . The composition of  claim 20 , wherein the pharmaceutically acceptable carrier comprises water, aqueous hyaluronic acid, saline, Ringer's solution, dextrose solution, Hank's solution, a buffer, or a nonaqueous vehicle. 
     
     
         22 . The composition of  claim 21 , wherein the buffer comprises a phosphate buffer, bicarbonate buffer, or Tris buffer. 
     
     
         23 . The composition of  claim 20 , wherein the composition is injectable. 
     
     
         24 . The composition of  claim 20 , wherein the composition is a liquid, gel, or paste. 
     
     
         25 . A method for treating or preventing wrinkles in a subject, the method comprising injecting the composition of  claim 1  at the site of an existing wrinkle in the subject or at a region of the subject that is susceptible to wrinkle formation. 
     
     
         26 . The use of the composition of  claim 1  as a dermal filler. 
     
     
         27 . A method for enhancing wound healing, the method comprising applying the composition of any one of  claims 1 - 24  at and/or near the site of the wound. 
     
     
         28 . A method for treating or preventing inflammation in a joint of a subject, the method comprising injecting the composition of any one of  claims 1 - 24  into the joint. 
     
     
         29 . A method for repairing and/or regrowing chondrocytes at an articular surface of a subject, the method comprising applying the composition of any one of  claims 1 - 24  to the articular surface. 
     
     
         30 . A method for treating or preventing inflammation at an articular surface of a subject, the method comprising applying the composition of any one of  claims 1 - 24  to the articular surface. 
     
     
         31 . A method for preventing or reducing scar formation on or near the spine after a surgical procedure, the method comprising applying to a subject the micronized composition of any one of  claims 1 - 24  directly to the spinal dura of the subject or a region near the spine. 
     
     
         32 . The method of  claim 31 , wherein the surgical procedure comprises a posterior procedure. 
     
     
         33 . The method of  claim 32 , wherein the posterior procedure is a laminectomy or discectomy. 
     
     
         34 . The method of  claim 32 , wherein the posterior procedure is an Anterior Lumbar Interbody Fusion (ALIF) or Transforaminal Interbody Fusion (TLIF). 
     
     
         35 . The method of  claim 31 , wherein the surgical procedure comprises an anterior procedure. 
     
     
         36 . A method for treating a dural tear in a subject, the method comprising applying directly to the dural tear the micronized composition of any one of  claims 1 - 24 . 
     
     
         37 . A method for promoting the healing of a wound in a subject, the method comprising applying to the wound the micronized composition of  claim 1 , wherein the wound is in the cranial dura, a wound resulting from a perioplastic procedure, for the elimination of a frenum pull, for the regeneration of lost patella tissue, for the repair of the Schneiderian membrane in the sinus cavity, or the soft tissue around dental implants. 
     
     
         38 . A method for promoting wound healing associated with a dental surgical procedure, wherein the method comprises contacting the wound with the composition of any one of  claims 1 - 24 . 
     
     
         39 . The method of  claim 38 , wherein the composition is used with dental implants, in the treatment of advanced gingival recession defect, or in guided tissue regeneration. 
     
     
         40 . A method for promoting wound healing associated with an orthopedic application, wherein the method comprises contacting the wound with the composition of any one of  claims 1 - 24 . 
     
     
         41 . The method of  claim 40 , wherein the composition is used in tendon repair, aiding in the repair of periostium, repairing ruptured/damaged bursa, or securing void filling materials during bone repair. 
     
     
         42 . A method for promoting wound healing associated with an ENT application, wherein the method comprises contacting the wound with the composition of any one of  claims 1 - 24 . 
     
     
         43 . A three-dimensional construct comprising the composition of any one of  claims 1 - 24 , wherein the composition is produced by a process comprising (1) treating micronized particles with a cross-linking agent and placing the treated particles in a mold or (2) admixing micronized particles with an adhesive and placing the admixture in a mold. 
     
     
         44 . The construct of  claim 43 , wherein the micronized particles comprise a micronized amnion/chorion tissue graft. 
     
     
         45 . The construct of  claim 43 , wherein the micronized particles comprise micronized amnion and intermediate tissue layer. 
     
     
         46 . The construct of  claim 43 , wherein the adhesive comprises a fibrin sealant, a cyanoacrylate, gelatin and thrombin products, polyethylene glycol polymers, albumin, gluteraldehyde, or any combination thereof. 
     
     
         47 . The construct of  claim 43 , wherein the construct further comprises one or more placental tissues affixed to the construct. 
     
     
         48 . The construct of  claim 47 , wherein the placental tissue comprises a layer of amnion, chorion, or a laminate of amnion and/or chorion. 
     
     
         49 . A topical composition comprising the micronized composition of any one of  claims 1 - 24  and a pharmaceutically acceptable carrier. 
     
     
         50 . The composition of  claim 49 , wherein the composition comprising micronized particles having a particle size from 20 μm to 100 μm. 
     
     
         51 . The composition of  claim 49 , wherein the composition comprising micronized particles at from 0.5% to 20% by weight of the topical composition. 
     
     
         52 . The composition of  claim 49 , wherein the composition comprising micronized particles at from 2% to 5% by weight of the topical composition. 
     
     
         53 . The composition of  claim 49 , wherein the pharmaceutically acceptable carrier comprises a surfactant, an emulsifier, or a combination thereof. 
     
     
         54 . The composition of  claim 49 , wherein the pharmaceutically acceptable carrier comprises a polyalkylene glycol. 
     
     
         55 . The composition of  claim 49 , wherein the pharmaceutically acceptable carrier comprises a mixture of polyalkylene glycol and a fatty alcohol. 
     
     
         56 . The composition of  claim 55 , wherein the polyalkylene glycol is polyethylene glycol and the fatty alcohol comprises capryl alcohol (1-octanol), 2-ethyl hexanol, pelargonic alcohol (1-nonanol), capric alcohol (1-decanol, decyl alcohol), undecyl alcohol (1-undecanol, undecanol, hendecanol), lauryl alcohol (dodecanol, 1-dodecanol), tridecyl alcohol (1-tridecanol, tridecanol, isotridecanol), myristyl alcohol (1-tetradecanol), pentadecyl alcohol (1-pentadecanol, pentadecanol), cetyl alcohol (1-hexadecanol), palmitoleyl alcohol (cis-9-hexadecen-1-ol), heptadecyl alcohol (1-n-heptadecanol, heptadecanol), stearyl alcohol (1-octadecanol), isostearyl alcohol (16-methylheptadecan-1-ol), elaidyl alcohol (9E-octadecen-1-ol), oleyl alcohol (cis-9-octadecen-1-ol), linoleyl alcohol (9Z, 12Z-octadecadien-1-ol), elaidolinoleyl alcohol (9E, 12E-octadecadien-1-ol), linolenyl alcohol (9Z, 12Z, 15Z-octadecatrien-1-ol) elaidolinolenyl alcohol (9E, 12E, 15-E-octadecatrien-1-ol), ricinoleyl alcohol (12-hydroxy-9-octadecen-1-ol), nonadecyl alcohol (1-nonadecanol), arachidyl alcohol (1-eicosanol), heneicosyl alcohol (1-heneicosanol), behenyl alcohol (1-docosanol), erucyl alcohol (cis-13-docosen-1-ol), lignoceryl alcohol (1-tetracosanol), ceryl alcohol (1-hexacosanol), montanyl alcohol, cluytyl alcohol (1-octacosanol), myricyl alcohol, melissyl alcohol (1-triacontanol), geddyl alcohol (1-tetratriacontanol), cetearyl alcohol, or any combination thereof. 
     
     
         57 . The composition of  claim 55 , wherein the polyalkylene glycol is polyethylene glycol and the fatty alcohol is cetyl alcohol. 
     
     
         58 . A method for treating wrinkles in a subject, the method comprising applying the composition of any one of  claims 49 - 58  on an existing wrinkle present on subject. 
     
     
         59 . A method for preventing wrinkles in a subject, the method comprising applying the composition of any one of  claims 49 - 58  on the skin of the subject that is prone to wrinkle formation. 
     
     
         60 . A method for enhancing re-epithelialization of the dermal skin layer, the method comprising applying the composition of any one of  claims 49 - 58  to the damaged epithelial layer present on the skin. 
     
     
         61 . A method for enhancing wound healing in a subject, the method comprising injecting the composition of any one of  claims 1 - 24  in or near the wound. 
     
     
         62 . The method of  claim 61 , wherein the composition is injected sub-cutaneously, sub-dermally, intramuscularly, or at the periosteal interface. 
     
     
         63 . The method of  claim 61 , wherein the wound is a diabetic ulcer, a superficial skin wound, tracking wound, or a wound derived from a repeated surgical procedure. 
     
     
         64 . The method of  claim 61 , wherein the wound is an incision site for the treatment of spinal scoliosis. 
     
     
         65 . An implantable medical device comprising the composition of any one of  claims 1 - 24 . 
     
     
         66 . A pharmaceutical composition comprising micronized amnion as the sole placental tissue component. 
     
     
         67 . Micronized placental tissue particles selected from the group consisting of amnion, chorion, intermediate tissue layer, or any combination thereof wherein the micronized placental tissue particles have a volume to surface area ratio of from about 0.06 μm to about 6×10 4  μm. 
     
     
         68 . Micronized placental tissue particles selected from the group consisting of amnion, chorion, intermediate tissue layer, or any combination thereof wherein the micronized particles have a particle size from about 0.05 μm to about 1 μm. 
     
     
         69 . An extract of micronized placental tissue particles selected from the group consisting of amnion, chorion, intermediate tissue layer, or any combination thereof, wherein the extract comprises one or more cytokines or one or more growth factors.